FIGURE 10.

(A) Structure optimization of FIIN-1. H-bonds are indicated by blue hashed lines. Hydrophobic interactions are outlined by hashed brown arc (PDB: 5B7V). The covalent bond-forming Michael acceptor carbon of the acrylamide is indicated by red arrow. (B) Discovery of irreversible inhibitors bearing novel pyrrolopyrimidine scaffold. (C) Discovery of 2H-pyrazolo [3,4-d]pyrimidine derivatives. Hydrophobic interaction region is outlined by hashed brown arc. Covalent binding region is highlighted by dashed red arc. (D) Covalent FGFR inhibitors bearing pyrazolo [3,4-d]pyridazinone.